a. Field of the Invention
This invention relates to novel pyranoindole derivatives, to a process and to intermediates for preparing the derivatives, to methods for using the derivatives and to compositions and therapeutically acceptable salts of the derivatives.
More specifically, the present invention relates to novel 1,3,4,9-tetrahydropyrano[3,4-b]indole or 1,3,4,9-tetrahydrothiopyrano3,4-b]indole derivatives having a hydroxyalkanamine or lower alkoxyalkanamine and a lower alkyl group at position 1. These derivatives are useful as diuretic agents in a mammal at dosages which do not elicit undesirable side effects. The combination of these attributes render the 1,3,4,9-tetrahydro(thio)pyrano[3,4-b]indole derivatives of this invention therapeutically useful.
The 1,3,4,9-tetrahydro(thio)pyrano[3,4-b]indole derivatives of this invention belong to a special class of diuretic agents which antagonize the renal effects of mineralocorticoids. As a result, these compounds are useful in treating hyperaldosteronism by increasing urine volume and sodium and chloride excretion without affecting potassium excretion. Therefore, these compounds find utility in the treatment of edema and hypertension.
b. Description of the Prior Art
A number of reports dealing with 1,3,4,9-tetrahydro(thio)pyrano[3,4-b]indole derivatives are available. For instance, a number of these derivatives are reported by C. A. Demerson et al., in U.S. Pat. No. 3,843,681, issued Oct. 22, 1974 and C. A. Demerson et al., in U.S. Pat. No. 3,880,853, issued Apr. 29, 1975.
The compounds of the present invention are distinguished from the compounds of the prior art by the nature of the substituents on the pyranoindole nucleus and by their pharmacologic properties. More specifically, the novel compounds of this invention are distinguished from the prior art compounds by having a hydroxyalkanamine or lower alkoxyalkanamine group at position 1 of the pyranoindole nucleus. In addition, the novel pyrano[3,4-b]indole or thiopyrano[3,4-b]indole derivatives of this invention possess useful diuretic activity in mammals, a pharmacologic activity not previously reported for pyrano[3,4-b]indole derivatives.